Endometriosis Knowledgebase

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Gene id

4843

Gene Summary Protein Summary Gene ontology KEGG pathways Diseases PubMed references

Gene Summary

Gene Symbol

NOS2 Gene UCSC Ensembl

Aliases

HEP-NOS, INOS, NOS, NOS2A

Gene name

nitric oxide synthase 2

Alternate names

nitric oxide synthase, inducible, NOS, type II, hepatocyte NOS, inducible NO synthase, inducible NOS, nitric oxide synthase 2, inducible, nitric oxide synthase 2A (inducible, hepatocytes), nitric oxide synthase, macrophage, peptidyl-cysteine S-nitrosylase NOS2,

Gene location

17q11.2 (27804338: 27756765) Exons: 29 NC_000017.11

Gene summary(Entrez)

Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM

163730

Protein Summary

Protein general information

P35228

Name: Nitric oxide synthase, inducible (EC 1.14.13.39) (Hepatocyte NOS) (HEP NOS) (Inducible NO synthase) (Inducible NOS) (iNOS) (NOS type II) (Peptidyl cysteine S nitrosylase NOS2)

Length: 1153 Mass: 131,117

Tissue specificity: Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets.

Sequence

MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPLVETGKKSPESLVKLD
ATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIMTPKSLTRGPRDKPTPPDELLPQAIEFVNQY
YGSFKEAKIEEHLARVEAVTKEIETTGTYQLTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFE
HICRHVRYSTNNGNIRSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVGGLEFPGCPFNGWYMG
TEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINIAVLHSFQKQNVTIMDHHSAAESFMKYMQNE
YRSRGGCPADWIWLVPPMSGSITPVFHQEMLNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFA
CMLMRKTMASRVRVTILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGDELSGQEDAFRSWAVQ
TFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDLSKALSSMHAKNVFTMRLKSRQNLQSPTSSR
ATILVELSCEDGQGLNYLPGEHLGVCPGNQPALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLS
QALTYFLDITTPPTQLLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCFVRNASGFHLPEDPSH
PCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPDEDHIYQEEMLEMAQKGVLHAVHTAYSRLPG
KPKVYVQDILRQQLASEVLRVLHKEPGHLYVCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHE
DIFGAVFPYEAKKDRVAVQPSSLEMSAL

Structural information

Protein Domains	Flavodoxin-like. (539-677) FAD-binding (730-970)
Interpro:	IPR003097 IPR017927 IPR001094 IPR008254 IPR001709 IPR029039 IPR004030 IPR001433 IPR017938
Prosite:	PS51384 PS50902 PS60001
Pfam:	PF00667 PF00258 PF00175 PF02898
PDB:	1NSI 2LL6 2NSI 3E7G 3EJ8 3HR4 4CX7 4NOS
PDBsum:	1NSI 2LL6 2NSI 3E7G 3EJ8 3HR4 4CX7 4NOS
DIP:	59359
STRING:	ENSP00000327251;

Other Databases

GeneCards: NOS2; Malacards: NOS2

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0001666	response to hypoxia	IEA	biological_process
GO:0001912	positive regulation of le ukocyte mediated cytotoxi city	TAS	biological_process
GO:0002227	innate immune response in mucosa	NAS	biological_process
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	TAS	molecular_function
GO:0005102	receptor binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005516	calmodulin binding	IEA	molecular_function
GO:0005622	intracellular	IDA	cellular_component
GO:0005634	nucleus	ISS	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005777	peroxisome	IDA	cellular_component
GO:0005829	cytosol	IMP	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006527	arginine catabolic proces s	IDA	biological_process
GO:0006801	superoxide metabolic proc ess	ISS	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0007263	nitric oxide mediated sig nal transduction	IBA	biological_process
GO:0007623	circadian rhythm	IEA	biological_process
GO:0009617	response to bacterium	NAS	biological_process
GO:0010181	FMN binding	ISS	molecular_function
GO:0010629	negative regulation of ge ne expression	IGI	biological_process
GO:0018119	peptidyl-cysteine S-nitro sylation	ISS	biological_process
GO:0020037	heme binding	ISS	molecular_function
GO:0030863	cortical cytoskeleton	IEA	cellular_component
GO:0031284	positive regulation of gu anylate cyclase activity	IBA	biological_process
GO:0032310	prostaglandin secretion	IDA	biological_process
GO:0034617	tetrahydrobiopterin bindi ng	ISS	molecular_function
GO:0034618	arginine binding	ISS	molecular_function
GO:0035690	cellular response to drug	IEA	biological_process
GO:0042127	regulation of cell prolif eration	IEA	biological_process
GO:0042177	negative regulation of pr otein catabolic process	IEA	biological_process
GO:0042742	defense response to bacte rium	ISS	biological_process
GO:0042742	defense response to bacte rium	IMP	biological_process
GO:0042803	protein homodimerization activity	ISS	molecular_function
GO:0043457	regulation of cellular re spiration	TAS	biological_process
GO:0045454	cell redox homeostasis	TAS	biological_process
GO:0045776	negative regulation of bl ood pressure	IBA	biological_process
GO:0045909	positive regulation of va sodilation	IBA	biological_process
GO:0046872	metal ion binding	IEA	molecular_function
GO:0048471	perinuclear region of cyt oplasm	IEA	cellular_component
GO:0050660	flavin adenine dinucleoti de binding	ISS	molecular_function
GO:0050661	NADP binding	TAS	molecular_function
GO:0050796	regulation of insulin sec retion	IMP	biological_process
GO:0050829	defense response to Gram- negative bacterium	NAS	biological_process
GO:0051712	positive regulation of ki lling of cells of other o rganism	IMP	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0071222	cellular response to lipo polysaccharide	IEA	biological_process
GO:0071346	cellular response to inte rferon-gamma	IEA	biological_process
GO:0072604	interleukin-6 secretion	IDA	biological_process
GO:0072606	interleukin-8 secretion	IDA	biological_process
GO:1900015	regulation of cytokine pr oduction involved in infl ammatory response	IDA	biological_process
GO:0001666	response to hypoxia	IEA	biological_process
GO:0001912	positive regulation of le ukocyte mediated cytotoxi city	TAS	biological_process
GO:0002227	innate immune response in mucosa	NAS	biological_process
GO:0004517	nitric-oxide synthase act ivity	IEA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IEA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IEA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	TAS	molecular_function
GO:0005102	receptor binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005516	calmodulin binding	IEA	molecular_function
GO:0005622	intracellular	IDA	cellular_component
GO:0005634	nucleus	ISS	cellular_component
GO:0005737	cytoplasm	IEA	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005777	peroxisome	IDA	cellular_component
GO:0005829	cytosol	IMP	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006527	arginine catabolic proces s	IEA	biological_process
GO:0006527	arginine catabolic proces s	IDA	biological_process
GO:0006801	superoxide metabolic proc ess	IEA	biological_process
GO:0006801	superoxide metabolic proc ess	ISS	biological_process
GO:0006809	nitric oxide biosynthetic process	IEA	biological_process
GO:0006809	nitric oxide biosynthetic process	IEA	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0007263	nitric oxide mediated sig nal transduction	IBA	biological_process
GO:0007623	circadian rhythm	IEA	biological_process
GO:0009617	response to bacterium	NAS	biological_process
GO:0010181	FMN binding	IEA	molecular_function
GO:0010181	FMN binding	IEA	molecular_function
GO:0010181	FMN binding	ISS	molecular_function
GO:0010629	negative regulation of ge ne expression	IEA	biological_process
GO:0010629	negative regulation of ge ne expression	IGI	biological_process
GO:0016491	oxidoreductase activity	IEA	molecular_function
GO:0016491	oxidoreductase activity	IEA	molecular_function
GO:0018119	peptidyl-cysteine S-nitro sylation	IEA	biological_process
GO:0018119	peptidyl-cysteine S-nitro sylation	ISS	biological_process
GO:0020037	heme binding	IEA	molecular_function
GO:0020037	heme binding	ISS	molecular_function
GO:0030863	cortical cytoskeleton	IEA	cellular_component
GO:0031284	positive regulation of gu anylate cyclase activity	IBA	biological_process
GO:0032310	prostaglandin secretion	IDA	biological_process
GO:0032496	response to lipopolysacch aride	IEA	biological_process
GO:0034617	tetrahydrobiopterin bindi ng	IEA	molecular_function
GO:0034617	tetrahydrobiopterin bindi ng	ISS	molecular_function
GO:0034618	arginine binding	IEA	molecular_function
GO:0034618	arginine binding	ISS	molecular_function
GO:0035690	cellular response to drug	IEA	biological_process
GO:0042127	regulation of cell prolif eration	IEA	biological_process
GO:0042177	negative regulation of pr otein catabolic process	IEA	biological_process
GO:0042742	defense response to bacte rium	IEA	biological_process
GO:0042742	defense response to bacte rium	ISS	biological_process
GO:0042742	defense response to bacte rium	IMP	biological_process
GO:0042803	protein homodimerization activity	IEA	molecular_function
GO:0042803	protein homodimerization activity	ISS	molecular_function
GO:0043457	regulation of cellular re spiration	TAS	biological_process
GO:0045454	cell redox homeostasis	TAS	biological_process
GO:0045776	negative regulation of bl ood pressure	IBA	biological_process
GO:0045909	positive regulation of va sodilation	IBA	biological_process
GO:0046872	metal ion binding	IEA	molecular_function
GO:0048471	perinuclear region of cyt oplasm	IEA	cellular_component
GO:0050660	flavin adenine dinucleoti de binding	IEA	molecular_function
GO:0050660	flavin adenine dinucleoti de binding	ISS	molecular_function
GO:0050661	NADP binding	TAS	molecular_function
GO:0050796	regulation of insulin sec retion	IMP	biological_process
GO:0050829	defense response to Gram- negative bacterium	NAS	biological_process
GO:0051712	positive regulation of ki lling of cells of other o rganism	IMP	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0071222	cellular response to lipo polysaccharide	IEA	biological_process
GO:0071346	cellular response to inte rferon-gamma	IEA	biological_process
GO:0072604	interleukin-6 secretion	IDA	biological_process
GO:0072606	interleukin-8 secretion	IDA	biological_process
GO:1900015	regulation of cytokine pr oduction involved in infl ammatory response	IDA	biological_process
GO:0001912	positive regulation of le ukocyte mediated cytotoxi city	TAS	biological_process
GO:0002227	innate immune response in mucosa	NAS	biological_process
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	IDA	molecular_function
GO:0004517	nitric-oxide synthase act ivity	TAS	molecular_function
GO:0005102	receptor binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005622	intracellular	IDA	cellular_component
GO:0005634	nucleus	ISS	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005737	cytoplasm	IDA	cellular_component
GO:0005777	peroxisome	IDA	cellular_component
GO:0005829	cytosol	IMP	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006527	arginine catabolic proces s	IDA	biological_process
GO:0006801	superoxide metabolic proc ess	ISS	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0006809	nitric oxide biosynthetic process	IDA	biological_process
GO:0007263	nitric oxide mediated sig nal transduction	IBA	biological_process
GO:0009617	response to bacterium	NAS	biological_process
GO:0010181	FMN binding	ISS	molecular_function
GO:0010629	negative regulation of ge ne expression	IGI	biological_process
GO:0018119	peptidyl-cysteine S-nitro sylation	ISS	biological_process
GO:0020037	heme binding	ISS	molecular_function
GO:0031284	positive regulation of gu anylate cyclase activity	IBA	biological_process
GO:0032310	prostaglandin secretion	IDA	biological_process
GO:0034617	tetrahydrobiopterin bindi ng	ISS	molecular_function
GO:0034618	arginine binding	ISS	molecular_function
GO:0042742	defense response to bacte rium	ISS	biological_process
GO:0042742	defense response to bacte rium	IMP	biological_process
GO:0042803	protein homodimerization activity	ISS	molecular_function
GO:0043457	regulation of cellular re spiration	TAS	biological_process
GO:0045454	cell redox homeostasis	TAS	biological_process
GO:0045776	negative regulation of bl ood pressure	IBA	biological_process
GO:0045909	positive regulation of va sodilation	IBA	biological_process
GO:0050660	flavin adenine dinucleoti de binding	ISS	molecular_function
GO:0050661	NADP binding	TAS	molecular_function
GO:0050796	regulation of insulin sec retion	IMP	biological_process
GO:0050829	defense response to Gram- negative bacterium	NAS	biological_process
GO:0051712	positive regulation of ki lling of cells of other o rganism	IMP	biological_process
GO:0072604	interleukin-6 secretion	IDA	biological_process
GO:0072606	interleukin-8 secretion	IDA	biological_process
GO:1900015	regulation of cytokine pr oduction involved in infl ammatory response	IDA	biological_process

KEGG pathways

hsa01100  Metabolic pathways
hsa05200  Pathways in cancer
hsa05152  Tuberculosis
hsa05145  Toxoplasmosis
hsa05142  Chagas disease
hsa04066  HIF-1 signaling pathway
hsa05146  Amoebiasis
hsa04371  Apelin signaling pathway
hsa05140  Leishmaniasis
hsa05222  Small cell lung cancer
hsa05133  Pertussis
hsa05132  Salmonella infection
hsa04020  Calcium signaling pathway
hsa04146  Peroxisome
hsa00330  Arginine and proline metabolism
hsa00220  Arginine biosynthesis

Diseases

Associated diseases	References
Alzheimer's disease	PMID: 19141999
Asthma	PMID: 19247692
Azoospermia	PMID: 22050043
Beta thalassemia	PMID: 19103526
Cerebral palsy	PMID: 18977990
Chronic obstructive pulmonary disease (COPD)	PMID: 19625176
Congenital bilateral absence of the vas deferens (CBAVD)	PMID: 11445485
Cystic fibrosis	PMID: 20028935
Diabetes	PMID: 19479237
Ectopic endometriosis	PMID: 11268729
Endometriosis	PMID: 11779590
Esophageal achalasia	PMID: 19337240
Esophageal cancer	KEGG: H00017
Hypertension	PMID: 19131662
Hypospermatogenesis	PMID: 15804870
Male infertility	PMID: 20684956
Maturation arrest (MA)	PMID: 15804870
Migraine disorders	PMID: 19559392
Multiple sclerosis	PMID: 19667218
Oligoasthenoteratozoospermia	PMID: 25744373
Oocyte competency	PMID: 24607880
Oocyte competency	PMID: 24607880
Endometriosis associated infertility	INFBASE16580392
Female infertility	INFBASE12372469
Endometriosis	INFBASE11779590
Adenomyosis	INFBASE11268729
Ectopic endometriosis	INFBASE11268729
Polycystic ovary syndrome (PCOS)	PMID: 23900753
Psoriasis	PMID: 20953189
Psychiatric disorders	PMID: 19086053
Rheumatoid arthritis	PMID: 19242068
Sertoli cell-only syndrome (SCOS)	PMID: 15804870
Spinal dysraphism	PMID: 19161160
Systemic lupus erythematosus	PMID: 19225544
Unexplained infertility	PMID: 16139338
Varicocele	PMID: 17346270

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes	Abstract
11268729	Endometrio sis			20 (6 cases of adenomyosis, 14 women with nor mal fecundity a s controls)	Female infertility	NOS	Show abstract
23935397	Endometrio sis			80 (40 patients with endometri osis, 40 withou t endometriosis )		TLR-2 TLR -9 NOD-1 NOD-2 and NOS	Show abstract
19531501	Endometrio sis	NOS3 (E298D)	Korean	758 (299 women with advanced s tage endometrio sis, 459 contro l women without endometriosis)		NOS	Show abstract
14667898	Endometrio sis	NOS (E298D)				NOS	Show abstract
12372469	Endometrio sis			39 (9 fertile w omen with regul ar cycles, 30 i nfertile women with varying se verity of endom etriosis)	Female infertility	NOS alpha(v)beta(3) integrin	Show abstract
16580392	Endometrio sis			49 (30 patients with endometri osis-associated infertility, 1 9 patients with carcinoma in s itu of the cerv ix)	Female infertility		Show abstract
11779590	Endometrio sis			18 (9 infertile women with end ometriosis, 9 n ormal fertile w omen)			Show abstract